Raynaud's disease (RD) and Raynaud's phenomenon (RP) are disorders having a prevalence of about 3% to more than 5% that affect peripheral blood vessels, involving brief episodes of vasospasm causing decreased blood flow to the fingers and toes, and rarely to the nose, ears, nipples, and lips. When this disorder occurs without any known cause, it is called Raynaud's disease, or primary Raynaud's. When the condition occurs along with a likely cause, it is known as Raynaud's phenomenon, or secondary Raynaud's. Raynaud's disease, most common in young women (60 to 90% of reported cases), is idiopathic. Raynaud's phenomenon is secondary to other conditions, such as connective tissue disorders, obstructive arterial diseases (arteriosclerosis obliterans, thromboangiitis obliterans, thoracic outlet syndrome), neurogenic lesions, drug intoxications (ergot, methysergide), dysproteinemias, myxedema, primary pulmonary hypertension, and trauma. Raynaud's phenomenon is commonly found associated with certain rheumatic diseases such as systemic sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. Secondary Raynaud's may also be a result of mechanical trauma, hand-arm vibration syndrome, paraprotinemias, and certain chemicals. Patients with secondary Raynaud's associated with rheumatic diseases often have autoantibodies such as a +ANA, +anti-centromere, and/or +anti-scl-70, and visible changes in their nailfold capillary pattern. As used herein, “Raynaud's” when used without a noun encompasses both Raynaud's disease and Raynaud's phenomenon.
Cold temperatures or stressful emotions can trigger attacks of either primary or secondary Raynaud's. In response to cold exposure, vasospasm in distal arteries and arterioles leads to blood being shunted from the extremities through the numerous arteriovenous anastomoses found in the digits. In response to heat, flow is decreased through these anastamoses and instead capillary flow is increased. The classical pattern consists of triphasic color changes of white (ischemia), blue or purple (cyanosis or deoxygenation), and red (reperfusion phase). The affected areas can throb or feel numb and tingly. With severe Raynaud's, prolonged or repeated episodes can cause prolonged pain, sores or tissue death (gangrene).
Since stressful emotions can trigger attacks of either primary or secondary Raynaud's, a central nervous system component is indicated as well as a peripheral vascular component.
There is no accepted standard method of measuring the severity of the disease or response to therapy. The attacks of Raynaud's are difficult to elicit, and the severity of the elicited attacks varies. Since many patients do not develop the full triphasic color changes, there is some controversy over proper diagnosis of the condition. In addition, complaints of sensation changes (cold, numbness, tingling, or pain) vary among patients these changes do not strictly correlate with the observed color differences.
Many different classes of drugs have been used to treat patients with Raynaud's. Much work has focused on vasodilators. Calcium channel blockers are the most commonly used class of vasodilators, and have been shown to be effective in several studies. However, many patients do not respond or cannot tolerate these drugs because of frequent adverse effects such as headache, flushing, and hypotension. Some studies have been carried out on other drugs that can improve vasodilation including angiotensin-II type I receptor antagonist, topical nitrates, serotonin antagonists, nonselective endothelin receptor antagonist, and phosphodiesterase inhibitors.
Studies have shown that the potent vasodilators, prostaglandins and prostacyclin analogs, are beneficial for treating severe Raynaud's. Unfortunately, prostaglandins and prostacyclin analogs are typically administered via intravenous infusion, necessitating hospitalization for their use. A few studies have examined the use of oral prostacyclin analogs, but mixed results have been reported with one study showing benefit, another showing no benefit over placebo. There have been only a few studies on the use of topical agents directly applied to the hands for the treatment of Raynaud's, and while some compositions have included prostanoids, most have involved nitrate compounds, such as glyceryl trinitrate, or minoxidil.
The prostacyclin analogue iloprost has been effective in secondary Raynaud's associated with scleroderma. alprostadil has been shown to be as effective as iloprost in a blind study, and was reported to improve severe digital ischemia associated with severe Raynaud's in another study. The prostanoids have been reported to have other effects besides vasodilation, including decreasing endothelial injury markers, which may imply an effect on reducing structural damage of vessel walls, decreasing neutrophil activation, inhibiting platelet aggregation, and modulating fibrinolytic activity. These agents may therefore have longer-term beneficial effects than that expected from their immediate vasodilatory effect. There have been reports of sustained benefit from use of these drugs; effects from a transdermal patch of PGE2 were reported to last at least 84 hours, and intravenous infusions of these agents have been reported to last from 30 days to 12 weeks.